High Homocysteine

Table of Contents

Summary

High homocysteine concentration in the blood is associated with an increased risk of cardiovascular disease (CVD). Therefore, homocysteine-lowering strategies are being investigated for their ability to reduce the risk of CVD. Nutrients involved in the metabolism of homocysteine include folate, vitamin B12, vitamin B6, riboflavin, and choline. Although supplementation with folate, vitamin B6, and vitamin B12 successfully lowers homocysteine concentration in the blood, no significant effect on CVD risk has been demonstrated. There is some evidence that riboflavin supplementation may lower homocysteine and blood pressure in individuals with a certain genetic predisposition. 

 

Condition Overview

Homocysteine is an amino acid that is an intermediate in the production of two other amino acids, methionine and cysteine. Although homocysteine is naturally present in our bodies, too much homocysteine in the blood has been associated with an increased risk of CVD, including venous thrombosis, atherosclerosis, high blood pressure, coronary heart disease, and stroke. Most research indicates that a plasma homocysteine level less than 10 micromoles/L is associated with a lower risk of CVD.

See below for specific information about nutrients and dietary factors relevant to high homocysteine.

 

Nutrition Research

diagram of homocysteine metabolism

Other Articles

Atherosclerosis

Coronary Heart Disease

High Blood Pressure

Stroke

Choline
 

What it does
General
  • Humans can synthesize small amounts of choline but not enough to support health. Therefore, choline is considered an essential nutrient and must be consumed in the diet.
  • Choline functions as a vital structural component of cell membranes and some proteins.
Homocysteine-specific
  • Choline is a precursor to betaine, a compound that participates in a reaction that converts homocysteine to methionine. Choline supplementation is therefore being investigated as a potential homocysteine-lowering strategy.
What we know
  • Dietary intake of choline and betaine were not associated with coronary heart disease risk in a large observational study conducted in middle-aged men and women.
  • Two preliminary randomized controlled trials indicated that supplementation with large doses of choline or betaine decreased plasma homocysteine levels in healthy men and CVD patients.
  • However, there is insufficient evidence to demonstrate that increased intake of choline affects CVD risk.

For references and more information, see the section on high homocysteine in the Choline article.  
 

Choline flashcard. Main functions: 1) structural component of all cell membranes, 2) transport and metabolism of fat and cholesterol, 3) helps make some important neurotransmitters, and 4) helps maintain normal levels of homocysteine in the blood. Good sources: egg (1 large), 147 mg; meat (beef and poultry), beef (3 ounces), 97 mg; seafood (fish and shellfish), scallop (steamed, 3 ounces) 94 mg (mg=milligrams; a three-ounce serving of meat or fish is about the size of a deck of cards; Daily Recommnedation: 550 mg for all men and 425 mg for all women; Special Notes: 1) Choline can be made in the body, but it is not enough to support health. Therefore, it must also be consumed in the diet. 2) A varied diet should provide enough choline for most people, but strict vegetarians who don't consume milk or eggs may be at risk of inadequate choline intake.

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Folate


What it does
General
  • Folate is a B-vitamin required for DNA synthesis and the formation of new cells.
  • Additionally, the B-vitamins folate, vitamin B12, and vitamin B6 work together to maintain normal concentrations of homocysteine.
What we know
  • Folate-rich diets are associated with a lower risk of cardiovascular disease (CVD), including coronary artery disease, heart attack, and stroke. 
  • Increased intake of folate from food or folic acid from supplements decreases homocysteine concentration in the blood.
  • Homocysteine-lowering therapy with supplemental B vitamins (folic acid, vitamin B6, and vitamin B12) may be particularly useful in lowering the risk of stroke but appears to have little utility in the prevention of other cardiovascular events.

For references and more information, see the section on Cardiovascular disease in the Folate article. 
 

Folate Flashcard. Main Functions: 1) required for DNA synthesis, 2) supports cell growth and repair, 3) helps prevent neural tube defects. Good Sources: legumes (beans, peas, lentils), lentils (cooked) one-half cup = 179 micrograms dietary folate equivalents (DFE); green leafy vegetables (kale, spinach), spinach (cooked) one-half cup, 131 micrograms DFE; fortified food and supplements, sliced bread (enriched), 1 slice, 84 micrograms DFE. Daily Recommendation: 400 micrograms DFE for adults, 600 micrograms DFE for pregnant women. Special Notes: 1) Folate is a general term that refers to both natural folates in food and folic acid, the synthetic form used in supplements and fortified food. 2) DFE = a unit of measure that accounts for differences in the absorption of naturally occurring food folate and synthetic folic acid. 3) To reduce the risk of neural tube defects, all women capable of becoming pregnant should consume 400 micrograms of folic acid daily in addition to the folate obtained from a varied diet. 4) Very high-dose folic acid supplementation (5,000 micrograms) can mask a vitamin B12 deficiency, specifically signs of nerve damage.

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Riboflavin


What it does
General
  • Riboflavin is a B-vitamin that assists several metabolic and antioxidant enzymes and helps convert food into usable energy.
Homocysteine-specific
  • By assisting the enzyme MTHFR, riboflavin helps convert folate to a form required for the transformation of homocysteine to methionine.
What we know
  • Individuals with a certain genetic variation (polymorphism) in MTHFR may have an increased risk of developing high blood pressure, cardiovascular disease, and cancer.
  • In hypertensive individuals with the MTHFR c.677C>T polymorphism (homozygotes), low-dose riboflavin supplementation lowers both homocysteine concentration and blood pressure.
Highlight

The MTHFR polymorphism is measured by genetic testing. In a genetic test, a small amount of blood, saliva, or tissue is used to isolate and determine an individual’s genetic information. Genetic testing is voluntary; doctors and genetic counselors can advise you on the decision to have this type of test.

Source: National Human Genome Research Institute

For more information, see the Riboflavin article.
 

Riboflavin (vitamin B2) Flashcard. Main Functions. (1) helps convert food into useable energy, and (2) assists several antioxidant enzymes. Good Sources. Dairy Products (milk, yogurt, cheese), milk (nonfat), 8 ounces, 0.45 mg; Meat (chicken, beef, fish), salmon, 3 ounces, 0.13 mg; Egg (1 large), 0.26 mg. A 3-ounce serving of meat or fish is about the size of a deck of cards. Daily Recommendation. 1.3 mg for men, 1.1 mg for women. Special Notes. (1) riboflavin is easily destroyed upon exposure to light. (2) Low-dose riboflavin supplementation may lower blood pressure in individuals with a genetic mutation in MTHFR, and enzyme involved in folate metabolism.

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Vitamin B6


What it does
General
  • Vitamin B6 helps convert food into usable energy and assists in the formation of neurotransmitters, red blood cells, and DNA.
  • Additionally, the B-vitamins folate, vitamin B12, and vitamin B6 work together to maintain normal concentrations of homocysteine.
What we know
  • Supplementation with vitamin B6 alone does not appear to lower homocysteine levels in the blood.
  • However, numerous randomized controlled trials have demonstrated that supplementation with a combination of vitamin B6, vitamin B12, and folic acid lowers homocysteine levels in individuals with vascular dysfunction or hyperhomocysteinemia.
  • Despite the homocysteine-lowering effect, vitamin B6 supplementation (in combination with vitamin B12 and folic acid), does not appear to have a strong influence on the prevention of cardiovascular events or on cardiovascular disease risk reduction.

For references and more information, see the section on homocysteine in the Vitamin B6 article. 
 

Vitamin B6 Flashcard. Main Functions: 1) helps convert food into energy, 2) helps make red blood cells, 3) helps maintain normal levels of homocysteine in the blood. Good Sources: Fish (slamon, tuna, halibut), wild salmon, 3 ounces, 0.5-0.8 mg; poultry (turkey, chicken, duck), light-meat turkey (cooked), 3 ounces = 0.7 mg; nuts (hazelnuts, walnuts) pistachio nuts, 1 ounce or 47 pistachios = 0.5 mg. Daily Recommendation: 2 mg for all adults. Special Notes: 1) The Daily Recommendation listed is specific to the LPI based on extensive review of the scientific evidence. The Institute of Medicine's Recommended Dietary Allowance (RDA) is 1.3 mg/day for adults 19-50 years, 1.7 mg/day for men 51 years and older, and 1.5 mg/day for women 51 years and older. 2) In the US, vitamin B6 is added back to refined grains. Therefore, enriched products are also a source of vitamin B6. 3) Excessive supplementation of vitamin B6 (more than 100 mg/day) can cause nerve damage and skin lesions.

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Vitamin B12


What it does
General
  • Vitamin B12 helps convert food into usable energy, make red blood cells, and is required for proper nerve function.
  • Additionally, the B-vitamins folate, vitamin B12, and vitamin B6 work together to maintain normal blood concentrations of homocysteine.
What we know
  • Vitamin B12 deficiency is common in individuals over 60 years of age and may contribute to elevated blood homocysteine.
  • While supplemental folic acid has the greatest homocysteine-lowering effect of the B-vitamins, co-supplementation of folic acid plus vitamin B12 can lower homocysteine levels even further.
  • In spite of the homocysteine-lowering effect, B-vitamin supplementation does not appear to have a strong influence on the prevention of cardiovascular events or on cardiovascular disease risk reduction.

For references and more information, see the section on homocysteine in the Vitamin B12 article. 
 

Vitamin B12 (cobalamin) Flashcard. Main Functions: 1) Helps make red blood cells, 2) Required for proper nerve function, and 3) Helps maintain normal levels of homocysteine in the blood. Good Sources: Vitamin B12 is only found in animal products. Seafood (shellfish, fish), clams (steamed) 3 ounces = 84 micrograms; poultry (turkey, chicken, duck), roasted turkey, 3 ounces = 0.8 micrograms; red meat (beef, pork, lamb), lean beef plate steak (grilled), 3 ounces = 6.9 micrograms. Daily Recommendation: adults 19-50 years = 2.4 micrograms; LPI recommends older adults (51 years and older) take 100-400 micrograms of supplemental vitamin B12. Special Notes: 1) Over-the-counter antacids reduce vitamin B12 absorption. 2) The capacity to absorb vitamin B12 from food goes down with age. 3) Symptoms of vitamin B12 deficiency include tingling and numbness in the extremities, nerve damage, and memory loss. 4) Older adults and individuals consuming a vegan diet should obtain vitamin B12 from supplements or fortified food.

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Coffee


What it does
General
  • Coffee is a complex mixture of chemicals. In addition to caffeine, coffee contains several phytochemicals that can influence human health.
What we know
  • Higher coffee intake has been associated with higher blood homocysteine concentration.
  • Randomized controlled trials have confirmed the homocysteine-raising effect of coffee intakes of about four cups/day.
  • Although coffee consumption increases blood homocysteine concentration, there appears to be no significant association between moderate coffee consumption (three to four cups/day) and the risk of coronary heart disease.

For references and more information, see the section on homocysteine in the Coffee article. 

Additional reference
  • Eilat-Adar S, et al., Nutritional Recommendations for Cardiovascular Disease Prevention. Nutrients. 2013;5:3546-683
     

Definitions

Metabolism - a biochemical transformation
Observational study - a human research study in which no experimental intervention or treatment is applied, and participants are simply observed over time
Placebo - a chemically inactive substance
Randomized controlled trial - a human research study in which participants are assigned by chance alone to receive either an experimental agent (the treatment group) or a placebo (the control group)
Venous thrombosis - a blood clot that forms in a vein

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Authors and Reviewers

Originally written in May 2015 by:
Giana Angelo, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in September 2015 by:
John F. Keaney, Jr., M.D.
Medical Director, Heart and Vascular Center of Excellence
Chief, Division of Cardiovascular Medicine
University of Massachusetts Medical School and Memorial Medical Center
Mary C. DeFeudis Professor of Biomedical Research
University of Massachusetts Medical School

Copyright 2015-2025  Linus Pauling Institute

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